I propose a group of projects having the general theme of the distribution and control of the pulmonary circulation in abnormal lungs. I have a special interest in hypoxic pulmonary vasoconstriction (HPV) as an autoregulatory mechanism which, by redistributing blood flow between abnormal and normal lung, protects the peripheral oxygen tension. I propose: 1) studies of the effects of inhalation anesthetic drugs and of hypocapnia on blood flow redistribution in man, in whom I will calculate intrapulmonary shunt by the oxygen method; 2) studies of variation in contralateral (a) airway pressure, (b) alveolar oxygen tension, and (c) vascular bed size as well as determine the mechanism of blood flow reduction through atelectatic lung in an animal model in which electromagnetic flowmeter probes are used to determine pulmonary blood flow distribution; and 3) an analysis of the interactions of hypoxia and vasoactive drugs with anesthetic drugs on pulmonary vascular smooth muscle strips, in vitro. Preliminary studies support our methods and hypotheses. I propose both carefully defined questions and open-ended investigations. Within the proposed grant period, however, we hope to define the role of active autoregulation of the pulmonary circulation in man, and quantitatively describe the major determinants of this process. The new information will directly improve the care of patients who have lung disease.